Atanackovic Djordje, Altorki Nasser K, Stockert Elisabeth, Williamson Barbara, Jungbluth Achim A, Ritter Erika, Santiago Darren, Ferrara Cathy A, Matsuo Mitsutoshi, Selvakumar Annamalai, Dupont Bo, Chen Yao-Tseng, Hoffman Eric W, Ritter Gerd, Old Lloyd J, Gnjatic Sacha
Ludwig Institute for Cancer Research, and Department of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Immunol. 2004 Mar 1;172(5):3289-96. doi: 10.4049/jimmunol.172.5.3289.
MAGE-3 is the most commonly expressed cancer testis Ag and thus represents a prime target for cancer vaccines, despite infrequent natural occurrence of MAGE-3-specific immune responses in vivo. We report in this study the successful induction of Ab, CD8(+), and CD4(+) T cells in nonsmall cell lung cancer patients vaccinated with MAGE-3 recombinant protein. Two cohorts were analyzed: one receiving MAGE-3 protein alone, and one receiving MAGE-3 protein with adjuvant AS02B. Of nine patients in the first cohort, three developed marginal Ab titers and another one had a CD8(+) T cell response to HLA-A2-restricted peptide MAGE-3 271-279. In contrast, of eight patients from the second cohort vaccinated with MAGE-3 protein and adjuvant, seven developed high-titered Abs to MAGE-3, and four had a strong concomitant CD4(+) T cell response to HLA-DP4-restricted peptide 243-258. One patient simultaneously developed CD8(+) T cells to HLA-A1-restricted peptide 168-176. The novel monitoring methodology used in this MAGE-3 study establishes that protein vaccination induces clear CD4(+) T cell responses that correlate with Ab production. This development provides the framework for further evaluating integrated immune responses in vaccine settings and for optimizing these responses for clinical benefit.
黑色素瘤抗原基因-3（MAGE-3）是最常表达的癌胚抗原，因此尽管在体内很少自然发生MAGE-3特异性免疫反应，但它仍是癌症疫苗的主要靶点。我们在这项研究中报告，用MAGE-3重组蛋白接种的非小细胞肺癌患者成功诱导了抗体、CD8(+)和CD4(+) T细胞。分析了两个队列：一个仅接受MAGE-3蛋白，另一个接受MAGE-3蛋白与佐剂AS02B。在第一个队列的9名患者中，3名患者产生了边缘抗体滴度，另一名患者对HLA-A2限制性肽MAGE-3 271-279有CD8(+) T细胞反应。相比之下，在接种MAGE-3蛋白和佐剂的第二个队列的8名患者中，7名患者产生了针对MAGE-3的高滴度抗体，4名患者对HLA-DP4限制性肽243-258有强烈的伴随CD4(+) T细胞反应。一名患者同时对HLA-A1限制性肽168-176产生了CD8(+) T细胞。在这项MAGE-3研究中使用的新型监测方法表明，蛋白疫苗接种可诱导与抗体产生相关的明显CD4(+) T细胞反应。这一进展为进一步评估疫苗环境中的综合免疫反应以及优化这些反应以获得临床益处提供了框架。
